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695 Efficacy and safety of trastuzumab deruxtecan (T-DXd) with durvalumab in patients with non-small cell lung cancer (HER2 altered NSCLC) who progressed on anti-PD1/PD-L1 therapy (HUDSON)
  1. Parneet Cheema1,
  2. Sylvia Hartl2,
  3. Marianna Koczywas3,
  4. Maximilian Hochmair4,
  5. Frances A Shepherd5,
  6. Quincy Chu6,
  7. Giuseppe Galletti7,
  8. Mark Gustavson8,
  9. Sonia Iyer9,
  10. J Carl Barrett9,
  11. Brent Evans8,
  12. Rakesh Kumar10,
  13. Jan Cosaert11,
  14. Keunchil Park12 and
  15. John V Heymach13
  1. 1University of Toronto, Toronto, ON, Canada
  2. 2Ludwig Boltzmann Institute for Lung Health and Sigmund Freud University, Vienna, Austria
  3. 3City of Hope National Medical Center, Duarte, CA, USA
  4. 4Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Vienna, Austria
  5. 5Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada
  6. 6University of Alberta, Edmonton, AB, Canada
  7. 7Weill Cornell Medicine, New York, NY, USA
  8. 8AstraZeneca, Gaithersburg, MD, USA
  9. 9AstraZeneca, Waltham, MA, USA
  10. 10AstraZeneca, Gaithersburg, MD, USA
  11. 11AstraZeneca, Cambridge, UK
  12. 12Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  13. 13The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background The HUDSON platform study (NCT03334617) explores investigational therapies in patients (pts) with NSCLC who progressed on immune checkpoint inhibitors (ICIs) to overcome immune resistance in the post-ICI setting. HUDSON allocated treatment based on biomarker selection or on time (<24 vs. ≥ 24 weeks) before progression on prior ICI. Here, we report on the results of Durvalumab (anti-PD-L1) + T-DXd (anti-HER2 antibody drug conjugate) treatment (module 6) in pts with HER2 overexpressing or HER2 mutant tumours.

Methods Pts had documented advanced/metastatic NSCLC with centrally confirmed HER2 overexpression (HER2e) or activating mutations (HER2m), received platinum-based therapy and progressed on prior ICI. Pts received durvalumab 1120 mg iv and T-DXd 5.4 mg/kg iv every 3 weeks until disease progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR) per RECIST 1.1 criteria; secondary endpoints included progression-free survival (PFS), overall survival (OS) and frequency of adverse events (AEs).

Results A total of 43 pts (HER2e n=23, HER2m n=20) started therapy between 23/6/2020 and 16/9/2021. Differences in main demographic and disease characteristics at study entry were observed between HER2e and HER2m pts (sex, smoking status, extent of disease, primary resistance to prior ICI; extended report of the characteristics at the conference). Confirmed ORR was 26.1% (80% CI, 14.3–41.3) in HER2e pts and 35% (80% CI, 20.7–51.8) in HER2m pts. Median PFS was 2.8 mo (80% CI, 2.2–5.5) in HER2e pts and 5.7 mo (80% CI, 5.5–6.5) in HER2m pts. Median OS was 9.5 mo (80% CI, 6.6–12.4) in the HER2e group and 10.6 mo (80% CI, 8.9-NC) in the HER2m group. Median duration of follow-up in censored subjects was 16.5 mo (range, 7.3–24.2) in the HER2e pts and 17.1 mo (range, 4.4–27.6) in HER2m pts. Grade (G) ≥3 treatment emergent AEs (TEAEs) occurred in 55% of all pts (61% of HER2e pts, 50% of HER2m pts); the most common G ≥3 AEs were pneumonitis (none were fatal), pulmonary embolism and anemia. All grade and G≥3 treatment-related pneumonitis occurred in 9.3% (8.7% of HER2e pts, 10% of HER2m pts) and in 7% (8.7% of HER2e pts, 5% of HER2m pts) of all pts, respectively.

Conclusions Durvalumab+T-DXd combination was tolerated and showed antitumor activity in HER2 altered NSCLC in the post-ICI setting, with a trend toward higher response in HER2m pts. The small sample size limits the overall conclusions of the study.

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